Clinical Trials /

A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

NCT04072458

Description:

This study evaluates the safety, pharmacokinetics, and efficacy of BP1002 (L-Bcl-2) antisense oligonucleotide in patients with advanced lymphoid malignancies. Up to 12 evaluable patients with a diagnosis of relapsed or refractory lymphoid malignancies are expected to participate.

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Peripheral T-Cell Lymphoma
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
  • Transformed Non-Hodgkin Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies
  • Official Title: A Phase 1 Clinical Trial to Study the Safety, Pharmacokinetics, and Efficacy of BP1002 (L-Bcl-2) Antisense Oligonucleotide in Patients With Advanced Lymphoid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: BP1002-101-Lymph
  • NCT ID: NCT04072458

Conditions

  • Mantle Cell Lymphoma
  • Peripheral T-cell Lymphoma (PTCL)
  • Cutaneous T-cell Lymphoma (CTCL)
  • Chronic Lymphocytic Leukemia (CLL)
  • Small Lymphocytic Lymphoma (SLL)
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Hodgkin Lymphoma
  • Waldenstrom Macroglobulinemia
  • DLBCL

Interventions

DrugSynonymsArms
L-Bcl-2 antisense oligonucleotideBP1002BP1002 monotherapy

Purpose

This study evaluates the safety, pharmacokinetics, and efficacy of BP1002 (L-Bcl-2) antisense oligonucleotide in patients with advanced lymphoid malignancies. Up to 12 evaluable patients with a diagnosis of relapsed or refractory lymphoid malignancies are expected to participate.

Trial Arms

NameTypeDescriptionInterventions
BP1002 monotherapyExperimentalL-Bcl-2 Antisense oligonucleotide (BP1002) is given in a sequential, dose escalation design. Starting dose is 20mg/m^2.
  • L-Bcl-2 antisense oligonucleotide

Eligibility Criteria

        Inclusion Criteria:

          1. Adults ≥18 years of age

          2. Patient has a life expectancy ≥ 3 month

          3. Patient has relapsed or refractory disease Relapsed lymphoma: Relapsed lymphoma is
             disease that has responded to treatment but then returns.

             Refractory lymphoma: Failure to achieve complete response at the end of therapy or
             progression within 6 months from completion of therapy

          4. Included Diseases

               -  DLBCL, including transformed lymphoma

               -  Mantle Cell Lymphoma

               -  PTCL

               -  CTCL

               -  CLL/SLL

               -  Follicular lymphoma

               -  Marginal zone lymphoma

               -  Hodgkin lymphoma (both classical and lymphocyte predominant)

               -  Waldenströms Macroglobulinemia

          5. Must has failed or is not a candidate for available therapies with reasonable
             likelihood of clinical benefit, which includes FDA approved products and standard of
             care regimens

          6. Therapy means at least three front lines of therapy including Hematopoeitic Stem Cell
             Transplant (HSCT and/or Chimeric Antigen Receptor (CAR) T cells, when applicable

          7. Females must be of non-childbearing potential, surgically sterile, postmenopausal, or
             practice adequate methods of contraception during the study

          8. Males must agree to use an adequate method of contraception during the study

          9. Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2

         10. Adequate hepatic and renal functions as defined by:

               -  Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper
                  limit of normal (ULN); and

               -  Total bilirubin ≤1.5 times ULN; and

               -  Estimated glomerular filtration rate (eGFR) of at least 50ml/min. These
                  estimations can be calculated using the following methods:

                    -  Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation

                    -  Cockcroft Gault equation

                    -  Modification of Diet in Renal Disease (MDRD study equation)

                    -  Creatinine clearance estimated by 24-hr urine collection for creatinine
                       clearance

         11. Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic
             treatment (with the exception of alopecia), based on Investigator assessment

         12. Willing and able to provide written informed consent

        Exclusion Criteria:

          1. Active non-hematologic malignancy other than lymphoid malignancies treated with
             immuno- or chemotherapy within the previous 12 months except active non-melanoma,
             non-invasive skin cancer will be allowed

          2. Known, active Central Nervous System (CNS) involvement of disease requiring
             intrathecal therapy. Note: Patients with a history of CNS disease may be allowed to
             participate based on at least 1 documented, negative spinal fluid assessment within 28
             days prior to Screening

          3. Patient eligible for high dose chemotherapy and autologous stem cell transplant

          4. Indolent non-Hodgkin lymphoma (iNHL)

          5. Patients at high risk of Tumor Lysis Syndrome (TLS)

             a. Bulky disease i. A unidimensional lesion greater than 10 cm and/or b. Lymphocyte
             count greater than 25,000 per µL

          6. Receipt of any anti-cancer therapy within 14 days prior to Cycle 1 Day 1 (C1D1)

          7. Uncontrolled active, untreated, or progressive infection

          8. Receipt of any investigational agent or on study treatment within 30 days prior to
             C1D1

          9. Females who are pregnant, test positive for pregnancy, or are breast-feeding during
             the Screening period, or intend to become pregnant or breast-feed during the course of
             the study or within 30 days after last dose of study drug

         10. Serious intercurrent medical or psychiatric illness which, in the opinion of the
             Investigator, would interfere with the ability of the participant to complete the
             study

         11. Active hepatitis B infection (based on positive surface antigen [HBsAg]), hepatitis C
             infection (based on Hepatitis C Virus (HCV) positive antibody [HCV Ab]), or human
             immunodeficiency virus (HIV-1 or HIV-2, based on positive antibody)

         12. Presence of concurrent conditions that, in the opinion of the Investigator and/or
             Medical Monitor, may compromise or interfere with any aspect of study conduct or
             interpretation of results. This includes, but is not limited to, unstable or
             uncontrolled angina, New York Heart Association (NYHA) class III or IV congestive
             heart failure, uncontrolled and sustained hypertension, clinically significant cardiac
             dysrhythmia or clinically significant baseline EKG abnormality (e.g., QTcF >470 msec)

         13. Within the past 6 months, has had any of the following: myocardial infarction,
             unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular
             accident or transient ischemic attack

         14. Uncontrolled seizure disorder

         15. Unable or unwilling to communicate or cooperate with the Investigator or follow the
             protocol for any reason.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Identify Dose Limiting Toxicity (DLT) of BP1002
Time Frame:30 days
Safety Issue:
Description:Identify DLT of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria

Secondary Outcome Measures

Measure:Determine evidence of tumor response by bone marrow aspirate
Time Frame:30 days
Safety Issue:
Description:Assess tumor response by evaluating bone marrow aspirate to determine complete response (CR), partial response (PR), or minor response (MR) using appropriate uniform response criteria as published by Response Evaluation Criteria in Lymphoma (RECIL) 2017, CLL guidelines, and International Workshop on Waldenström's Macroglobulinemia (IWWM 6th)
Measure:Determine evidence of tumor response by Complete Blood Count (CBC)
Time Frame:30 days
Safety Issue:
Description:Assess tumor response by evaluating CBC measurements to determine complete response (CR), partial response (PR), or minor response (MR) using appropriate uniform response criteria as published by Response Evaluation Criteria in Lymphoma (RECIL) 2017, CLL guidelines, and International Workshop on Waldenström's Macroglobulinemia (IWWM 6th)
Measure:Determine estimates for time to progression (TTP)
Time Frame:30 days
Safety Issue:
Description:Measured from treatment start date to date of progression by CBC and/or bone marrow aspirate
Measure:Determine estimates for progression-free survival (PFS)
Time Frame:30 days
Safety Issue:
Description:Measured from treatment start date to date of progression or death by CBC and/or bone marrow aspirate
Measure:Determine estimates for event-free survival (EFS)
Time Frame:30 days
Safety Issue:
Description:Measured from treatment start date to date of progression, death, or change in therapy by CBC and/or bone marrow aspirate
Measure:Activity of BP1002 on Bcl-2 expression in tumor samples
Time Frame:30 days
Safety Issue:
Description:Flow cytometric assays to determine the effects of BP1002 on Bcl-2 protein expression using patient blood samples

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bio-Path Holdings, Inc.

Last Updated

September 9, 2020